Trial Outcomes & Findings for Study to Evaluate the Long-Term Safety, Tolerability and Efficacy of Dalfampridine. (NCT NCT02422940)

Last Updated: 2019-01-22

Results Overview

This extension study was designed to evaluate long-term safety, tolerability, and efficacy of dalfampridine-ER (extended release) in adult subjects with chronic post-ischemic stroke walking deficits. Subjects who had completed the placebo-controlled DALF-PS-1016 core study were eligible to enroll regardless of whether they had received active drug or placebo in the core study.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

294 participants

Primary outcome timeframe

up to 12 months

Results posted on

2019-01-22

Participant Flow

Participant milestones

Participant milestones
Measure	Dalfampridine-ER 7.5 mg Dalfampridine-ER 7.5 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 7.5 mg	Dalfampridine-ER 10 mg Dalfampridine-ER 10 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 10 mg
Overall Study STARTED	152	142
Overall Study COMPLETED	31	21
Overall Study NOT COMPLETED	121	121

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study to Evaluate the Long-Term Safety, Tolerability and Efficacy of Dalfampridine.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dalfampridine-ER 7.5 mg n=152 Participants Dalfampridine-ER 7.5 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 7.5 mg	Dalfampridine-ER 10 mg n=142 Participants Dalfampridine-ER 10 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 10 mg	Total n=294 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	152 Participants n=5 Participants	142 Participants n=7 Participants	294 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	62.1 years STANDARD_DEVIATION 10.87 • n=5 Participants	64.6 years STANDARD_DEVIATION 10.32 • n=7 Participants	63.3 years STANDARD_DEVIATION 10.67 • n=5 Participants
Sex: Female, Male Female	54 Participants n=5 Participants	50 Participants n=7 Participants	104 Participants n=5 Participants
Sex: Female, Male Male	98 Participants n=5 Participants	92 Participants n=7 Participants	190 Participants n=5 Participants
Region of Enrollment Canada	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Region of Enrollment United States	144 Participants n=5 Participants	133 Participants n=7 Participants	277 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 12 months

Population: The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment

Outcome measures

Outcome measures
Measure	Dalfampridine-ER 7.5 mg n=151 Participants Dalfampridine-ER 7.5 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 7.5 mg	Dalfampridine-ER 10 mg n=142 Participants Dalfampridine-ER 10 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 10 mg
The Primary Objective Was to Evaluate Serious and Non-serious Adverse Events for Study Participants as a Measure of Safety and Tolerability of Dalfampridine ER (Extended Release) for at Least 12-months. Subjects with at Least One TEAE	102 Participants	99 Participants
The Primary Objective Was to Evaluate Serious and Non-serious Adverse Events for Study Participants as a Measure of Safety and Tolerability of Dalfampridine ER (Extended Release) for at Least 12-months. Subjects with at Least One Serious TEAE	14 Participants	8 Participants
The Primary Objective Was to Evaluate Serious and Non-serious Adverse Events for Study Participants as a Measure of Safety and Tolerability of Dalfampridine ER (Extended Release) for at Least 12-months. Subjects by Maximum Severity (Mild)	45 Participants	45 Participants
The Primary Objective Was to Evaluate Serious and Non-serious Adverse Events for Study Participants as a Measure of Safety and Tolerability of Dalfampridine ER (Extended Release) for at Least 12-months. Subjects by Maximum Severity (Moderate)	43 Participants	43 Participants
The Primary Objective Was to Evaluate Serious and Non-serious Adverse Events for Study Participants as a Measure of Safety and Tolerability of Dalfampridine ER (Extended Release) for at Least 12-months. Subjects by Maximum Severity (Severe)	14 Participants	11 Participants
The Primary Objective Was to Evaluate Serious and Non-serious Adverse Events for Study Participants as a Measure of Safety and Tolerability of Dalfampridine ER (Extended Release) for at Least 12-months. Subjects with at least One TEAEA leading to Discon	12 Participants	7 Participants
The Primary Objective Was to Evaluate Serious and Non-serious Adverse Events for Study Participants as a Measure of Safety and Tolerability of Dalfampridine ER (Extended Release) for at Least 12-months. Subjects who Died Due to a TEAE	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1, up to 12 months

Population: The study was conducted in patients with chronic walking deficits from an ischemic stroke.

2 Minute Walk Test (2MinWT) and Change from Baseline by Visit

Outcome measures

Outcome measures
Measure	Dalfampridine-ER 7.5 mg n=146 Participants Dalfampridine-ER 7.5 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 7.5 mg	Dalfampridine-ER 10 mg n=136 Participants Dalfampridine-ER 10 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 10 mg
Change From Baseline on the Two-Minute Walk Test (2MinWT) Baseline	309.59 Feet Standard Deviation 132.956	297.41 Feet Standard Deviation 143.722
Change From Baseline on the Two-Minute Walk Test (2MinWT) Visit 2 (Day 15) Actual Value	319.24 Feet Standard Deviation 135.072	312.08 Feet Standard Deviation 146.818
Change From Baseline on the Two-Minute Walk Test (2MinWT) Visit 2 (Day 15) Change from Baseline	9.72 Feet Standard Deviation 34.898	14.27 Feet Standard Deviation 34.824
Change From Baseline on the Two-Minute Walk Test (2MinWT) Visit 3 (Month 1) Actual Value	322.95 Feet Standard Deviation 136.511	317.96 Feet Standard Deviation 146.419
Change From Baseline on the Two-Minute Walk Test (2MinWT) Visit 3 (Month 1) Change from Baseline	10.81 Feet Standard Deviation 40.457	14.48 Feet Standard Deviation 39.961
Change From Baseline on the Two-Minute Walk Test (2MinWT) Visit 4 (Month 2) Actual Value	328.01 Feet Standard Deviation 139.437	318.98 Feet Standard Deviation 147.429
Change From Baseline on the Two-Minute Walk Test (2MinWT) Visit 4 (Month 2) Change from Baseline	16.67 Feet Standard Deviation 34.512	17.48 Feet Standard Deviation 37.385
Change From Baseline on the Two-Minute Walk Test (2MinWT) Visit 5 (Month 3) Actual Value	323.29 Feet Standard Deviation 136.815	331.77 Feet Standard Deviation 140.872
Change From Baseline on the Two-Minute Walk Test (2MinWT) Visit 5 (Month 3) Change from Baseline	15.44 Feet Standard Deviation 41.635	16.99 Feet Standard Deviation 41.207
Change From Baseline on the Two-Minute Walk Test (2MinWT) Visit 6 (Month 6) Actual Value	335.28 Feet Standard Deviation 128.117	321.28 Feet Standard Deviation 133.484
Change From Baseline on the Two-Minute Walk Test (2MinWT) Visit 6 (Month 6) Change from Baseline	16.38 Feet Standard Deviation 38.767	72 Feet Standard Deviation 10.00
Change From Baseline on the Two-Minute Walk Test (2MinWT) Visit 7 (Month 9) Actual Value	312.98 Feet Standard Deviation 136.536	342.24 Feet Standard Deviation 129.673
Change From Baseline on the Two-Minute Walk Test (2MinWT) Visit 7 (Month 9) Change from Baseline	21.88 Feet Standard Deviation 45.327	19.25 Feet Standard Deviation 33.597
Change From Baseline on the Two-Minute Walk Test (2MinWT) Visit 8 (Month 12) Actual Value	330.07 Feet Standard Deviation 144.749	360.90 Feet Standard Deviation 107.895
Change From Baseline on the Two-Minute Walk Test (2MinWT) Visit 8 (Month 12) Change from Baseline	23.65 Feet Standard Deviation 50.899	19.98 Feet Standard Deviation 34.067
Change From Baseline on the Two-Minute Walk Test (2MinWT) Final Visit - Actual Value	320.34 Feet Standard Deviation 136.425	318.48 Feet Standard Deviation 126.718
Change From Baseline on the Two-Minute Walk Test (2MinWT) Final Visit - Change from Baseline	20.23 Feet Standard Deviation 50.991	9.88 Feet Standard Deviation 51.867

SECONDARY outcome

Timeframe: Day 1, up to 12 months

Population: The study was conducted in patients with chronic walking deficits from an ischemic stroke.

10 Meter Walk Test (10MWT) and Change from Baseline by Visit

Outcome measures

Outcome measures
Measure	Dalfampridine-ER 7.5 mg n=146 Participants Dalfampridine-ER 7.5 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 7.5 mg	Dalfampridine-ER 10 mg n=136 Participants Dalfampridine-ER 10 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 10 mg
Change From Baseline on the 10 Meter Walk Test (10MWT) Baseline	0.92 Meter /second Standard Deviation 0.454	0.89 Meter /second Standard Deviation 0.472
Change From Baseline on the 10 Meter Walk Test (10MWT) Visit 2 (Day 15) Actual Value	0.97 Meter /second Standard Deviation 0.498	0.94 Meter /second Standard Deviation 0.494
Change From Baseline on the 10 Meter Walk Test (10MWT) Visit 2 (Day 15) Change from Baseline	0.05 Meter /second Standard Deviation 0.118	0.05 Meter /second Standard Deviation 0.124
Change From Baseline on the 10 Meter Walk Test (10MWT) Visit 3 (Month 1) Actual Value	0.96 Meter /second Standard Deviation 0.470	0.98 Meter /second Standard Deviation 0.494
Change From Baseline on the 10 Meter Walk Test (10MWT) Visit 3 (Month 1) Change from Baseline	0.03 Meter /second Standard Deviation 0.124	0.06 Meter /second Standard Deviation 0.122
Change From Baseline on the 10 Meter Walk Test (10MWT) Visit 4 (Month 2) Actual Value	0.99 Meter /second Standard Deviation 0.502	0.98 Meter /second Standard Deviation 0.503
Change From Baseline on the 10 Meter Walk Test (10MWT) Visit 4 (Month 2) Change from Baseline	0.06 Meter /second Standard Deviation 0.136	0.08 Meter /second Standard Deviation 0.134
Change From Baseline on the 10 Meter Walk Test (10MWT) Visit 5 (Month 3) Actual Value	0.95 Meter /second Standard Deviation 0.489	1.00 Meter /second Standard Deviation 0.488
Change From Baseline on the 10 Meter Walk Test (10MWT) Visit 5 (Month 3) Change from Baseline	0.05 Meter /second Standard Deviation 0.146	0.08 Meter /second Standard Deviation 0.167
Change From Baseline on the 10 Meter Walk Test (10MWT) Visit 6 (Month 6) Actual Value	1.01 Meter /second Standard Deviation 0.497	0.99 Meter /second Standard Deviation 0.456
Change From Baseline on the 10 Meter Walk Test (10MWT) Visit 6 (Month 6) Change from Baseline	0.06 Meter /second Standard Deviation 0.145	0.07 Meter /second Standard Deviation 0.124
Change From Baseline on the 10 Meter Walk Test (10MWT) Visit 7 (Month 9) Actual Value	0.99 Meter /second Standard Deviation 0.582	1.06 Meter /second Standard Deviation 0.400
Change From Baseline on the 10 Meter Walk Test (10MWT) Visit 7 (Month 9) Change from Baseline	0.08 Meter /second Standard Deviation 0.205	0.08 Meter /second Standard Deviation 0.145
Change From Baseline on the 10 Meter Walk Test (10MWT) Visit 8 (Month 12) Actual Value	1.05 Meter /second Standard Deviation 0.563	1.08 Meter /second Standard Deviation 0.414
Change From Baseline on the 10 Meter Walk Test (10MWT) Visit 8 (Month 12) Change from Baseline	0.07 Meter /second Standard Deviation 0.198	0.06 Meter /second Standard Deviation 0.238
Change From Baseline on the 10 Meter Walk Test (10MWT) Final Visit - Actual Value	1.04 Meter /second Standard Deviation 0.534	0.91 Meter /second Standard Deviation 0.425
Change From Baseline on the 10 Meter Walk Test (10MWT) Final Visit - Change from Baseline	0.04 Meter /second Standard Deviation 0.199	-0.03 Meter /second Standard Deviation 0.263

SECONDARY outcome

Timeframe: Day 1, up to 12 months

Population: The study was conducted in patients with chronic walking deficits from an ischemic stroke.

The TUG measures mobility and balance and can predict the risk of falls. This test, which was initially called the Get-up and Go test, is considered a measure of dynamic balance. The subject is asked to stand up from a chair, walk 10 feet at a comfortable pace, turn around and be seated. The Timed Up and Go (TUG) is measured in seconds. There will be one practice test and then the timed test. Only the timed test will be analyzed at each visit time point. Reciprocal transformation may be performed if the time values are markedly skewed.

Outcome measures

Outcome measures
Measure	Dalfampridine-ER 7.5 mg n=146 Participants Dalfampridine-ER 7.5 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 7.5 mg	Dalfampridine-ER 10 mg n=136 Participants Dalfampridine-ER 10 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 10 mg
Change From Baseline on the Timed up and Go (TUG) Test Baseline	17.92 Seconds Standard Deviation 19.899	20.16 Seconds Standard Deviation 18.587
Change From Baseline on the Timed up and Go (TUG) Test Visit 2 (Day 15) Actual Value	18.59 Seconds Standard Deviation 30.461	19.82 Seconds Standard Deviation 20.019
Change From Baseline on the Timed up and Go (TUG) Test Visit 2 (Day 15) Change from Baseline	0.67 Seconds Standard Deviation 12.640	-0.40 Seconds Standard Deviation 4.844
Change From Baseline on the Timed up and Go (TUG) Test Visit 3 (Month 1) Actual Value	17.28 Seconds Standard Deviation 21.165	18.76 Seconds Standard Deviation 19.267
Change From Baseline on the Timed up and Go (TUG) Test Visit 3 (Month 1) Change from Baseline	-0.59 Seconds Standard Deviation 3.215	-0.61 Seconds Standard Deviation 7.329
Change From Baseline on the Timed up and Go (TUG) Test Visit 4 (Month 2) Actual Value	17.57 Seconds Standard Deviation 22.351	18.49 Seconds Standard Deviation 16.563
Change From Baseline on the Timed up and Go (TUG) Test Visit 4 (Month 2) Change from Baseline	-0.45 Seconds Standard Deviation 3.644	-1.32 Seconds Standard Deviation 4.816
Change From Baseline on the Timed up and Go (TUG) Test Visit 5 (Month 3) Actual Value	18.10 Seconds Standard Deviation 26.829	17.39 Seconds Standard Deviation 16.509
Change From Baseline on the Timed up and Go (TUG) Test Visit 5 (Month 3) Change from Baseline	0.05 Seconds Standard Deviation 7.321	-1.60 Seconds Standard Deviation 4.323
Change From Baseline on the Timed up and Go (TUG) Test Visit 6 (Month 6) Actual Value	17.75 Seconds Standard Deviation 31.394	17.07 Seconds Standard Deviation 15.532
Change From Baseline on the Timed up and Go (TUG) Test Visit 6 (Month 6) Change from Baseline	0.33 Seconds Standard Deviation 9.273	-1.36 Seconds Standard Deviation 4.740
Change From Baseline on the Timed up and Go (TUG) Test Visit 7 (Month 9) Actual Value	22.93 Seconds Standard Deviation 39.918	15.85 Seconds Standard Deviation 14.085
Change From Baseline on the Timed up and Go (TUG) Test Visit 7 (Month 9) Change from Baseline	1.66 Seconds Standard Deviation 11.085	-1.08 Seconds Standard Deviation 3.452
Change From Baseline on the Timed up and Go (TUG) Test Visit 8 (Month 12) Actual Value	16.80 Seconds Standard Deviation 13.724	15.17 Seconds Standard Deviation 15.635
Change From Baseline on the Timed up and Go (TUG) Test Visit 8 (Month 12) Change from Baseline	0.33 Seconds Standard Deviation 4.536	-0.50 Seconds Standard Deviation 2.606
Change From Baseline on the Timed up and Go (TUG) Test Final Visit - Actual Value	17.38 Seconds Standard Deviation 15.967	19.21 Seconds Standard Deviation 20.596
Change From Baseline on the Timed up and Go (TUG) Test Final Visit - Change from Baseline	1.34 Seconds Standard Deviation 6.416	1.25 Seconds Standard Deviation 6.914

SECONDARY outcome

Timeframe: Day 1, up to 12 months

Population: The study was conducted in patients with chronic walking deficits from an ischemic stroke.

The Walk-12 is a 12-question questionnaire that asks subjects to rate limitations of their mobility during the preceding two weeks on a 5-point scale (from 1= not at all to 5=extremely). For each visit, the Walk-12 score will be calculated by summing the 12 components and transforming into a scale with a range of 0 to 100. A higher score indicates a greater degree of limitation in walking. A negative change indicates an improvement in walking. 0 = no limitation in mobility to 100 extreme limitation in mobility. Walk-12 Score = 100 \* \[(Mean of the 12 items) - 1\]/(5-1)

Outcome measures

Outcome measures
Measure	Dalfampridine-ER 7.5 mg n=146 Participants Dalfampridine-ER 7.5 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 7.5 mg	Dalfampridine-ER 10 mg n=136 Participants Dalfampridine-ER 10 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 10 mg
Change From Baseline on the Walking Impact Scale (Walk-12) Baseline	47.37 units on a scale Standard Deviation 26.933	49.78 units on a scale Standard Deviation 26.583
Change From Baseline on the Walking Impact Scale (Walk-12) Visit 2 (Day 15) Actual Value	47.00 units on a scale Standard Deviation 25.860	45.95 units on a scale Standard Deviation 25.275
Change From Baseline on the Walking Impact Scale (Walk-12) Visit 2 (Day 15) Change from Baseline	-0.57 units on a scale Standard Deviation 13.081	-3.92 units on a scale Standard Deviation 14.235
Change From Baseline on the Walking Impact Scale (Walk-12) Visit 6 (Month 6) Actual Value	42.72 units on a scale Standard Deviation 23.649	48.14 units on a scale Standard Deviation 25.484
Change From Baseline on the Walking Impact Scale (Walk-12) Visit 6 (Month 6) Change from Baseline	-1.95 units on a scale Standard Deviation 13.247	-2.40 units on a scale Standard Deviation 14.457
Change From Baseline on the Walking Impact Scale (Walk-12) Visit 8 (Month 12) Actual Value	45.47 units on a scale Standard Deviation 23.405	49.67 units on a scale Standard Deviation 24.501
Change From Baseline on the Walking Impact Scale (Walk-12) Visit 8 (Month 12) Change from Baseline	-6.13 units on a scale Standard Deviation 16.047	-5.75 units on a scale Standard Deviation 12.986
Change From Baseline on the Walking Impact Scale (Walk-12) Final Visit - Actual Value	44.21 units on a scale Standard Deviation 24.976	49.00 units on a scale Standard Deviation 25.078
Change From Baseline on the Walking Impact Scale (Walk-12) Final Visit - Change from Baseline	-9.18 units on a scale Standard Deviation 17.097	-1.90 units on a scale Standard Deviation 12.530

SECONDARY outcome

Timeframe: Day 1, up to 12 months

Population: The study was conducted in patients with chronic walking deficits from an ischemic stroke.

The SIS consists of 59 items grouped in 8 domains: strength, hand function, activities of daily living (ADL) / instrumental activities of daily living (IADL), mobility, communication, emotion, memory and thinking, and participation/role function. The subject is asked to rate the level of difficulty in performing each item in the preceding week. Each item is scored on a 5-point scale ranging from 1 (inability to complete the item) to 5 (no difficulty experienced at all). For each domain, the SIS score will be calculated by summing all the items within the domain and transforming into a scale with a range of 0 to 100 as follows: SIS Score = 100 \* \[(Actual raw score - Lowest possible raw score)/ (Highest possible raw score-Lowest possible raw score)\].

Outcome measures

Outcome measures
Measure	Dalfampridine-ER 7.5 mg n=146 Participants Dalfampridine-ER 7.5 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 7.5 mg	Dalfampridine-ER 10 mg n=136 Participants Dalfampridine-ER 10 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 10 mg
Change From Baseline on the Stroke Impact Scale (SIS) SIS ADL/IADL - Baseline	71.8 score on a scale Standard Deviation 18.38	75.1 score on a scale Standard Deviation 16.56
Change From Baseline on the Stroke Impact Scale (SIS) SIS ADL/IADL Visit 6 Actual	72.8 score on a scale Standard Deviation 18.57	77.0 score on a scale Standard Deviation 16.14
Change From Baseline on the Stroke Impact Scale (SIS) SIS ADL/IADL Visit 6 Change from Baseline	0.4 score on a scale Standard Deviation 9.13	-0.2 score on a scale Standard Deviation 8.99
Change From Baseline on the Stroke Impact Scale (SIS) SIS ADL/IADL Visit 8 Actual	72.3 score on a scale Standard Deviation 18.64	73.8 score on a scale Standard Deviation 15.14
Change From Baseline on the Stroke Impact Scale (SIS) SIS ADL/IADL Visit 8 Change from Baseline	1.7 score on a scale Standard Deviation 10.49	-0.3 score on a scale Standard Deviation 8.35
Change From Baseline on the Stroke Impact Scale (SIS) SIS Communication - Baseline	88.6 score on a scale Standard Deviation 16.76	88.3 score on a scale Standard Deviation 17.81
Change From Baseline on the Stroke Impact Scale (SIS) SIS Communication Visit 6 Actual	88.7 score on a scale Standard Deviation 16.43	88.6 score on a scale Standard Deviation 15.38
Change From Baseline on the Stroke Impact Scale (SIS) SIS Communication Visit 6 Change from Baseline	-0.1 score on a scale Standard Deviation 9.85	0.3 score on a scale Standard Deviation 11.87
Change From Baseline on the Stroke Impact Scale (SIS) SIS Communication Visit 8 Actual	83.6 score on a scale Standard Deviation 22.74	89.7 score on a scale Standard Deviation 16.47
Change From Baseline on the Stroke Impact Scale (SIS) SIS Communication Visit 8 Change from Baseline	-1.2 score on a scale Standard Deviation 12.33	-2.5 score on a scale Standard Deviation 8.97
Change From Baseline on the Stroke Impact Scale (SIS) SIS Emotion - Baseline	67.3 score on a scale Standard Deviation 13.08	68.9 score on a scale Standard Deviation 13.16
Change From Baseline on the Stroke Impact Scale (SIS) SIS Emotion Visit 6 Actual	66.5 score on a scale Standard Deviation 12.88	65.7 score on a scale Standard Deviation 12.08
Change From Baseline on the Stroke Impact Scale (SIS) SIS Emotion Visit 6 Change from Baseline	-1.01 score on a scale Standard Deviation 15.56	-2.7 score on a scale Standard Deviation 14.26
Change From Baseline on the Stroke Impact Scale (SIS) SIS Emotion Visit 8 Actual	64.5 score on a scale Standard Deviation 14.94	67.0 score on a scale Standard Deviation 14.37
Change From Baseline on the Stroke Impact Scale (SIS) SIS Emotion Visit 8 Change from Baseline	-2.6 score on a scale Standard Deviation 12.77	3.8 score on a scale Standard Deviation 13.48
Change From Baseline on the Stroke Impact Scale (SIS) SIS Hand Function - Baseline	45.9 score on a scale Standard Deviation 34.01	48.4 score on a scale Standard Deviation 34.79
Change From Baseline on the Stroke Impact Scale (SIS) SIS Hand Function Visit 6 Actual	47.3 score on a scale Standard Deviation 34.81	52.3 score on a scale Standard Deviation 32.30
Change From Baseline on the Stroke Impact Scale (SIS) SIS Hand Function Visit 6 Change from Baseline	4.6 score on a scale Standard Deviation 17.57	1.3 score on a scale Standard Deviation 14.51
Change From Baseline on the Stroke Impact Scale (SIS) SIS Hand Function Visit 8 Actual	46.2 score on a scale Standard Deviation 34.66	54.0 score on a scale Standard Deviation 31.95
Change From Baseline on the Stroke Impact Scale (SIS) SIS Hand Function Visit 8 Change from Baseline	4.3 score on a scale Standard Deviation 20.12	3.3 score on a scale Standard Deviation 16.40
Change From Baseline on the Stroke Impact Scale (SIS) SIS Memory & Thinking - Baseline	82.8 score on a scale Standard Deviation 19.45	82.8 score on a scale Standard Deviation 19.91
Change From Baseline on the Stroke Impact Scale (SIS) SIS Memory & Thinking Visit 6 Actual	84.0 score on a scale Standard Deviation 19.32	84.9 score on a scale Standard Deviation 17.35
Change From Baseline on the Stroke Impact Scale (SIS) SIS Memory & Thinking Visit 6 Change from Baseline	0.9 score on a scale Standard Deviation 9.10	0.9 score on a scale Standard Deviation 10.86
Change From Baseline on the Stroke Impact Scale (SIS) SIS Memory & Thinking Visit 8 Actual	80.7 score on a scale Standard Deviation 20.51	87.1 score on a scale Standard Deviation 17.83
Change From Baseline on the Stroke Impact Scale (SIS) SIS Memory & Thinking Visit 8 Change from Baseline	0.5 score on a scale Standard Deviation 10.95	-1.0 score on a scale Standard Deviation 12.39
Change From Baseline on the Stroke Impact Scale (SIS) SIS Mobility - Baseline	71.7 score on a scale Standard Deviation 18.98	72.8 score on a scale Standard Deviation 19.07
Change From Baseline on the Stroke Impact Scale (SIS) SIS Mobility Visit 6 Actual	74.5 score on a scale Standard Deviation 18.52	74.2 score on a scale Standard Deviation 18.59
Change From Baseline on the Stroke Impact Scale (SIS) SIS Mobility Visit 6 Change from Baseline	1.4 score on a scale Standard Deviation 9.76	-0.9 score on a scale Standard Deviation 11.58
Change From Baseline on the Stroke Impact Scale (SIS) SIS Mobility Visit 8 Actual	70.8 score on a scale Standard Deviation 16.66	68.6 score on a scale Standard Deviation 19.46
Change From Baseline on the Stroke Impact Scale (SIS) SIS Mobility Visit 8 Change from Baseline	3.5 score on a scale Standard Deviation 13.56	-2.2 score on a scale Standard Deviation 11.17
Change From Baseline on the Stroke Impact Scale (SIS) SIS Participation - Baseline	64.8 score on a scale Standard Deviation 26.08	68.8 score on a scale Standard Deviation 22.85
Change From Baseline on the Stroke Impact Scale (SIS) SIS Participation Visit 6 Actual	69.6 score on a scale Standard Deviation 24.73	70.7 score on a scale Standard Deviation 21.95
Change From Baseline on the Stroke Impact Scale (SIS) SIS Participation Visit 6 Change from Baseline	3.4 score on a scale Standard Deviation 20.03	1.4 score on a scale Standard Deviation 15.97
Change From Baseline on the Stroke Impact Scale (SIS) SIS Participation Visit 8 Actual	65.3 score on a scale Standard Deviation 23.95	65.8 score on a scale Standard Deviation 24.65
Change From Baseline on the Stroke Impact Scale (SIS) SIS Participation Visit 8 Change from Baseline	4.3 score on a scale Standard Deviation 18.86	-3.1 score on a scale Standard Deviation 19.26
Change From Baseline on the Stroke Impact Scale (SIS) SIS Physical Dimension Score (SIS 16) - Baseline	63.6 score on a scale Standard Deviation 10.01	64.5 score on a scale Standard Deviation 9.94
Change From Baseline on the Stroke Impact Scale (SIS) SIS Physical Dimension Visit 6 Actual	65.1 score on a scale Standard Deviation 10.14	65.1 score on a scale Standard Deviation 9.66
Change From Baseline on the Stroke Impact Scale (SIS) SIS Physical Dim. Visit 6 Change from Baseline	0.7 score on a scale Standard Deviation 5.13	-0.6 score on a scale Standard Deviation 5.31
Change From Baseline on the Stroke Impact Scale (SIS) SIS Physical Dimension Visit 8 Actual	64.0 score on a scale Standard Deviation 9.52	62.8 score on a scale Standard Deviation 9.72
Change From Baseline on the Stroke Impact Scale (SIS) SIS Physical Dim. Visit 8 Change from Baseline	1.5 score on a scale Standard Deviation 6.73	-1.3 score on a scale Standard Deviation 4.92
Change From Baseline on the Stroke Impact Scale (SIS) SIS Strength - Baseline	53.4 score on a scale Standard Deviation 23.02	53.3 score on a scale Standard Deviation 22.34
Change From Baseline on the Stroke Impact Scale (SIS) SIS Strength Visit 6 Actual	51.5 score on a scale Standard Deviation 24.46	52.8 score on a scale Standard Deviation 21.25
Change From Baseline on the Stroke Impact Scale (SIS) SIS Strength Visit 6 Change from Baseline	-0.9 score on a scale Standard Deviation 15.85	0.0 score on a scale Standard Deviation 19.45
Change From Baseline on the Stroke Impact Scale (SIS) SIS Strength Visit 8 Actual	48.5 score on a scale Standard Deviation 19.16	51.8 score on a scale Standard Deviation 21.54
Change From Baseline on the Stroke Impact Scale (SIS) SIS Strength Visit 8 Change from Baseline	-1.1 score on a scale Standard Deviation 17.91	-1.3 score on a scale Standard Deviation 22.27
Change From Baseline on the Stroke Impact Scale (SIS) Stroke Recovery - Baseline	60.3 score on a scale Standard Deviation 21.42	65.0 score on a scale Standard Deviation 17.03
Change From Baseline on the Stroke Impact Scale (SIS) Stroke Recovery - Visit 6 Actual	64.0 score on a scale Standard Deviation 20.72	66.4 score on a scale Standard Deviation 17.19
Change From Baseline on the Stroke Impact Scale (SIS) Stroke Recovery Visit 6 Change from Baseline	2.8 score on a scale Standard Deviation 15.08	1.5 score on a scale Standard Deviation 12.08
Change From Baseline on the Stroke Impact Scale (SIS) Stroke Recovery Visit 8 Actual	62.4 score on a scale Standard Deviation 22.16	67.4 score on a scale Standard Deviation 18.03
Change From Baseline on the Stroke Impact Scale (SIS) Stroke Recovery Visit 8 Change from Baseline	0.6 score on a scale Standard Deviation 13.16	1.8 score on a scale Standard Deviation 13.32

SECONDARY outcome

Timeframe: Visit 8 (Month 12)

Population: The study was conducted in patients with chronic walking deficits from an ischemic stroke. These were the only participants to finish the SGI study due to study termination.

The Subject Global Impression (SGI) is single item measure of treatment response that asks the subject to rate the effects of the investigational drug on his or her overall walking ability using a 7 point scale ranging from 1 = "Terrible" to 7 = "Delighted."

Outcome measures

Outcome measures
Measure	Dalfampridine-ER 7.5 mg n=33 Participants Dalfampridine-ER 7.5 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 7.5 mg	Dalfampridine-ER 10 mg n=24 Participants Dalfampridine-ER 10 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 10 mg
Subject Global Impression (SGI) 2 - Unhappy	1 Participants	0 Participants
Subject Global Impression (SGI) 7 - Delighted	6 Participants	2 Participants
Subject Global Impression (SGI) 6 - Pleased	7 Participants	8 Participants
Subject Global Impression (SGI) 5 - Somewhat Satisfied	6 Participants	8 Participants
Subject Global Impression (SGI) 4 - Neutral/Mixed	12 Participants	5 Participants
Subject Global Impression (SGI) 3 - Somewhat Dissatisfied	1 Participants	0 Participants
Subject Global Impression (SGI) 1 - Terrible	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 1, up to 12 months

Population: The study was conducted in patients with chronic walking deficits from an ischemic stroke.

The SF-12 v2 (4-week recall) is a general health-related quality-of-life profile measure consisting of 12 items. The SF-12 Physical Component Summary (PCS) and the Mental Component Summary (MCS) scores will be derived and normed to a general United States population for score algorithm. The normalized PCS and MCS scores will be calculated at baseline, Month 12, and subsequent visits. SF-12 is a Physical and Mental Health Composite Scores (PCS \& MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.

Outcome measures

Outcome measures
Measure	Dalfampridine-ER 7.5 mg n=146 Participants Dalfampridine-ER 7.5 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 7.5 mg	Dalfampridine-ER 10 mg n=136 Participants Dalfampridine-ER 10 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 10 mg
Change From Baseline on the 12-item Health Survey (SF-12) MCS - Baseline	54.2 score on a scale Standard Deviation 11.26	54.4 score on a scale Standard Deviation 10.00
Change From Baseline on the 12-item Health Survey (SF-12) MCS - Visit 8 - (Month 12) Actual	50.5 score on a scale Standard Deviation 11.83	54.5 score on a scale Standard Deviation 11.60
Change From Baseline on the 12-item Health Survey (SF-12) MCS - Visit 8 - (Month 12) Change from Baseline	-4.3 score on a scale Standard Deviation 10.48	-2.4 score on a scale Standard Deviation 9.28
Change From Baseline on the 12-item Health Survey (SF-12) PCS - Baseline	36.2 score on a scale Standard Deviation 9.11	37.0 score on a scale Standard Deviation 8.64
Change From Baseline on the 12-item Health Survey (SF-12) PCS - Visit 8 - (Month 12) Actual	37.3 score on a scale Standard Deviation 8.12	34.4 score on a scale Standard Deviation 10.55
Change From Baseline on the 12-item Health Survey (SF-12) PCS - Visit 8 - (Month 12) Change from Baseline	2.7 score on a scale Standard Deviation 7.42	-2.3 score on a scale Standard Deviation 7.50

Adverse Events

Dalfampridine-ER 7.5 mg

Serious events: 14 serious events

Other events: 102 other events

Deaths: 1 deaths

Dalfampridine-ER 10 mg

Serious events: 8 serious events

Other events: 99 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Holy Roberts, Executive Medical Director - Medical Affairs

Acorda Therapeutics

Phone: 914-326-5224

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding the study results for a period up to 30 days from the date the communication is submitted to the sponsor. The sponsor shall have the right to defer proposed publication an additional 60 days from the end of the review period. The sponsor cannot require changes to the communication and cannot unilaterally extend the embargo.
Publication restrictions are in place

Restriction type: OTHER

Measure	Dalfampridine-ER 7.5 mg n=151 participants at risk Dalfampridine-ER 7.5 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 7.5 mg	Dalfampridine-ER 10 mg n=142 participants at risk Dalfampridine-ER 10 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. dalfampridine-ER 10 mg
Cardiac disorders Acute Myocardial Infarction	0.66% 1/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.00% 0/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.
Cardiac disorders Angina Unstable	0.66% 1/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.00% 0/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.
Cardiac disorders Antrial Fibrillation	0.00% 0/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.70% 1/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.
Cardiac disorders Coronary Artery Disease	0.66% 1/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.00% 0/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.
Cardiac disorders Myocardial Infarction	0.66% 1/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.00% 0/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.
General disorders Asthenia	0.66% 1/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.00% 0/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.
Infections and infestations Cellutiis	0.66% 1/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.70% 1/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.
Infections and infestations Escherichia Urinary Tract Infection	0.00% 0/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.70% 1/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.
Injury, poisoning and procedural complications Humerus Fracture	0.66% 1/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.00% 0/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.
Injury, poisoning and procedural complications Post Procedural Complication	0.66% 1/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.00% 0/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.
Musculoskeletal and connective tissue disorders Back Pain	0.66% 1/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.00% 0/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.70% 1/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal Cell Carcinoma	0.00% 0/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.70% 1/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid Cancer	0.00% 0/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.70% 1/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.
Nervous system disorders Convulsion	1.3% 2/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.70% 1/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.
Nervous system disorders Complex Partial Seizures	0.66% 1/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.00% 0/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.
Nervous system disorders Ischaemic Stroke	0.66% 1/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.00% 0/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.
Nervous system disorders Transient Ischaemic Attack	0.66% 1/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.00% 0/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.
Renal and urinary disorders Renal Failure Acute	0.00% 0/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.70% 1/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.
Vascular disorders Peripheral Arterial Occlusive Disease	0.66% 1/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.00% 0/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.
Gastrointestinal disorders Gastrointestinal Haemorrhage	0.00% 0/151 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.	0.70% 1/142 • Date collected within 1 year. The Safety Population of 293 subjects included all subjects who received at least one dose of study treatment. \*One subject was randomized but discontinued the study prior to receiving double-blind study treatment.